柯萨奇病毒性心肌炎小鼠基质金属蛋白酶与血管紧张素Ⅱ关系的研究(英文)

Study of the relationship with matrix metalloproteinases and angiotensinⅡ in mice with Coxsackievirus myocarditis

目的探讨柯萨奇病毒性心肌炎(VM)小鼠基质金属蛋白酶-3(MMP-3)及金属蛋白酶组织抑制因子-1(TI MP-1)与血管紧张素Ⅱ(AngⅡ)的关系。方法57只鼠龄4~6周Balb/c纯种雄性小鼠随机分为4组,对照组(A组,n=12)、模型组(B组,n=15)、假干预组(C组,n=15)、福辛普利组(D组,n=15)。B^D组小鼠腹腔接种0·1mL的Coxsakievirus B3(CVB3)病毒悬液建立VM模型,A组腹腔注射不含CVB3的0·1mL Hep-2细胞冻溶液作为对照组。C组及D组于注射CVB324h后分别给予生理盐水和福辛普利灌胃治疗,于第28天断颈处死小鼠,氯氨T法测定心肌胶原含量;放射免疫法检测血浆AngⅡ含量;逆转录-聚合酶链反应法(RT-PCR)检测心肌MMP-3、TI MP-1mRNA的表达。结果B组及C组血浆AngⅡ含量显著增高,心肌MMP-3表达显著上调,TI MP-1表达显著下调,心肌胶原含量显著增高(与A组比较,P<0·05);D组血浆AngⅡ含量显著下降,心肌MMP-3表达显著下调,TI MP-1表达显著上调,心肌胶原含量显著减少(与B组比较,P<0·05)。结论VM小鼠心肌MMP-3、TI MP-1mRNA表达与血浆AngⅡ变化密切相关,可能是导致心肌胶原重构的重要因素;福辛普利通过抑制AngⅡ的产生使心肌MMP-3mRNA表达显著下调、TI MP-1表达显著上调、心肌胶原含量显著减少。

Objective To explore the relationship of myocardial matrix metalloproteinase-3 （MMP-3）, tissue inhibitor of metalloproteinase-1 （TIMP-1） with angiotensin Ⅱ （AngⅡ） in mice with Coxsackievirus myoearditis （VM）.Methods Fifty-seven four to sixweek-old male Balb/c mice were divided into five groups randomly： group A, B, C and D. Mice in infected group （B--D, n =45） were inoculated intrapritoneaUy with 0. 1 ml of Coxsackievirus B3 （CVB3 Nancy strain）. Group A （control, n = 12） were inoculated intrapritoneally with 0.1 ml of Hep-2＇s solution. After 24h of inoculation, group C and D were treated with normal saline and fosinopril respectively. All mice were sacrificed on day 28. Myocardial collagen amount was measured by determination of hydroxyproline quantification, the Ang Ⅱ contents in plasma was measured by radioimmunoassay, and the mRNA expression of MMP-3 and TIMP-1 were detected by reverse transcription-polymerase chain reaction （RT-PCR） .Results In group B and C, Ang Ⅱ contents in plasma increased remarkably, the mRNA expression of MMP-3 was upregulated significantly and the mRNA expression of TIMP-1 was downregulated remarkably compared with those in group A （P〈0.05）. The myocardial collagen amount in group B and group C increased significantly compared with controls. In group D, AngⅡ contents in plasma decreased remarkably, the mRNA expression of MMP-3 was downregulated signifieantly and the mRNA expression of TIMP-1 was upregnlated remarkably compared with those in group B （P〈0.05）. The myocardial collagen amount in group D decreased significantly compared with those in group B.Conclusion The mRNA expression of MMP-3 and TIMP-1 was closely correlated with the changes of the AnglI contents in plasma of VM mice, and may contributes to myocardial collagen remodeling. These effects that the mRNA expression of MMP-3 was downregulated and TIMP-1 was upregulated significantly may be responsible for the effect of fusinopril on inhibiting the ang Ⅱ, and therefore the myocardial collagen amount decreased remarkably.